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The experience of chronic generalized harassment from others can have a deleterious impact on individuals over time. Specifically, coping resources may be taxed, resulting in the use of avoidant coping strategies such as substance use. However, little is known about the experience of chronic generalized harassment (e.g., verbal hostility, manipulation by others, exclusion from important events) and its impact on substance use in collegiate populations. In the current study, we examined the latent growth of generalized harassment across the transition from high school to college, whether this growth was heterogeneous, and the relationships between latent generalized harassment classifications and substance use. Incoming freshmen students (N = 2890; 58% female; 53% white) at eight colleges in Illinois completed a web survey at five points: fall 2011 (baseline), spring 2012 (T1), fall 2012 (T2), fall 2013 (T3) and fall 2014 (T4). Students were required to be at least 18 years old at baseline, and were compensated with online gift certificates. Two-part latent class growth analysis was implemented in order to examine heterogeneous growth over time. The results supported a two-class solution (infrequent and chronic classes) for generalized harassment. Growth in harassment was characterized by a decrease from baseline through college entry, with a recovery in rates by T3. Members of the chronically harassed class had greater mean generalized harassment over time, and were less likely to report zero instances of harassment experiences. As hypothesized, membership in the chronic class predicted future binge drinking, drinking to intoxication, problems due to alcohol use, and cigarette use, but not marijuana use. Future interventions should focus on providing college students with resources to help cope with distress stemming from persistent generalized harassment from peers, faculty, and other individuals in higher-education settings.